title: Efficient delivery of siRNA by atelocollagen in a murine laser-induced choroidal neovascularization model.
abstract: OBJECTIVE
  Previous studies have shown that small interfering RNAs (siRNAs) could suppress angiogenesis via stimulation of toll-like receptor-3 (TLR3). The purpose of this study was to determine the efficacy of atelocollagen to deliver siRNA without TLR3 stimulation in the laser-induced choroidal neovascularization (CNV) model.
  
  
  METHODS
  CNV was induced by laser injury in C57BL/6J mice and volumes were measured 7 days later. Nontargeted siRNA, 21-nucleotide (nt) siRNA-Luc (Luciferase) and 21-nt siRNA-Vegfa were injected into the vitreous following injury. Atelocollagen was incubated with naked 21-nt siRNAs before injection. To block TLR3 endosomal activity, chloroquine was injected intravitreously after laser injury.
  
  
  RESULTS
  The mean CNV volumes were significantly smaller in the naked siRNA-Luc, naked siRNA-Vegfa, or siRNA-Vegfa/atelocollagen complex compared with PBS, atelocollagen or siRNA-Luc/atelocollagen complex-injected mice (p < 0.05).
  
  
  CONCLUSIONS
  These findings demonstrate that atelocollagen may deliver siRNA without nonspecific TLR3 stimulation in the murine laser-CNV model.
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Ito
authors.forename: Miho
authors.initials: M
authors.lastname: Nozaki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sugitani
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ashikari
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirano
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ogura
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000008:administration & dosage* / Q000378:metabolism; D004195:Disease Models, Animal; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000378:metabolism; D058449:Intravitreal Injections; D017075:Laser Coagulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D051196:Toll-Like Receptor 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D000962:Antimalarials; D004337:Drug Carriers; D034741:RNA, Small Interfering; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D042461:Vascular Endothelial Growth Factor A; C059821:atelocollagen; D007371:Interferon-gamma; D002738:Chloroquine; D003094:Collagen